Pancreatitis Objectives: At the end of the two lectures the students will be able to: 1. Recognize the predisposing factors of pancreatitis. 2. Describe the different types of pancreatitis. 3. Understand the pathogenesis of acute and chronic pancreatitis.. Important note: Please check out this link before viewing the file to know if there are any additions ​ ​ or changes. The same link will be used for all of our work: Pathology Edit. ​ ​ Red: Important Grey: Extra notes 1 Mind maps: 2 Introduction: Anatomy of the pancreas: The pancreas is a transversely oriented retroperitoneal organ extending from the C loop of the duodenum to the hilum of the spleen.1 The pancreas is in reality two organs in one: ​ 1. 90% exocrine (involved in digestion by secretion of digestive enzymes). ​ - Its dysfunction usually results in problems with digestion & absorption, and the released hydrolytic enzymes will cause tissue destruction (usually exocrine is damaged first). ​ ​ 2. 10% endocrine (secretes hormones e.g. insulin ) - Its dysfunction will cause diabetes. Pancreatitis: Definition: Pancreatitis encompasses a group of disorders characterized by inflammation of the pancreas. ​ ​ ​ Clinical manifestations: can range in severity from a mild, self-limited disease2 to a severe and life ​ ​ ​ threatening acute inflammatory process. Duration: range from a transient attack to an irreversible loss of function. ​ Types: 1. Acute pancreatitis: gland can return to normal if underlying cause of the pancreatitis is removed. ​ 2. By contrast, Chronic pancreatitis: is defined by irreversible destruction of exocrine pancreatic ​ ​ ​ ​ parenchyma “the endocrine part may involved later”. NOTE: both entities ”acute and chronic” share similar pathogenic mechanisms, and indeed recurrent acute ​ ​ pancreatitis can result in chronic pancreatitis (in a chronic pancreatitis an acute attack can occur). ​ ​ 1 The retroperitoneal location of the pancreas and the generally vague nature of signs and symptoms associated with its injury or dysfunction allow many pancreatic diseases to progress undiagnosed for extended periods of time. 2 The patient may does not even know that he had an onset. 3 Acute pancreatitis Acute pancreatitis: is a group of reversible lesions characterized by inflammation of the pancreas ranging ​ ​ ​ ​ in severity from focal edema and fat necrosis to parenchymal necrosis with severe hemorrhage. Etiology: Common factors Less common Obstruction of the pancreatic duct system3: ➢ 80% of cases in Western countries are - eg. periampullary tumors, congenital cystic associated with one of two conditions: dilatation of the common bile duct, alcoholism, biliary tract disease. ​ ​ ​ biliary"sludge"4, and parasites (particularly 5 6 ➢ Gallstones are present in 35% to 60% of cases Ascarasis lumbricoides and Clonorchis sinensis ​ ​ ​ of acute pancreatitis. organisms). - Roughly 5% of patients with gallstones Medications: More than 85 drugs have been develop acute pancreatitis, and gallstones ​ reported to cause acute pancreatitis. These include are implicated in 35% to 60% of cases thiazide diuretics, azathioprine(immunosuppressant), overall. ​ ​ ​ estrogens, etc. Metabolic disorders: including ​ ​ hypertriglyceridemia, hyperparathyroidism, and other hypercalcemic states. Ca “enzyme activator” → ​ will cause premature activation of trypsin → activation of other pancreatic enzyme” → pancreatitis. Infectious: - Mumps. - Coxsackievirus. - Mycoplasma pneumoniae. Acute ischemia: induced by vascular thrombosis, ​ embolism, vasculitis (polyarteritis nodosa) and shock. Trauma: both blunt trauma and iatrogenic injury ​ (caused by a doctor) during surgery or endoscopic ​ ​ retrograde cholangiopancreatography7. Genetic: such as mutations in SPINK1 and PRSS1. ​ 3 Non-gallstones related obstructions. 4 A mixture of particulate solids that derived from bile.Ex:cholesterol crystals,calcium salts). 5 Associated with poor personal hygiene, poor sanitation, and in places where human feces are used as fertilizer. 6 People become infected when eating the parasite containing cysts within infected raw or undercooked fish. 7 Specialized technique used to study the bile ducts, pancreatic duct and gallbladder. ​ 4 Morphology: It ranges from: Inflammation and edema ⇒ severe extensive necrosis and hemorrhage. The basic alterations are: Mnemonic: MIND ​ - M= Microvascular leakage → edema. ​ - I= Acute Inflammatory reaction. ​ ​ ​ - N= lipolytic enzymes → fat necrosis ​ - D=Protease → Destruction of pancreatic parenchyma. ​ ​ ​ - Elastase → hemorrhage. ​ ​ Fat necrosis, results from enzymatic destruction of fat cells; The released fatty acids⇒ combine with ​ ​ ​ calcium⇒ form insoluble salts that precipitate in situ (in same place it was formed). ​ ​ ​ ​ *Dystrophic calcification (calcification occurring in degenerated or necrotic tissue). ​ ​ Pathogenesis: ​ 8 Autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes . ​ ​ Thus, activation of trypsinogen9 is an important triggering event in acute pancreatitis. ​ ​ If trypsin is inappropriately generated from its proenzyme trypsinogen, it can activate itself as well as other pro enzymes (e.g., phospholipases and elastases) that can then take part in the process of autodigestion. The pathways that can lead to the enzyme activation are: 8 The pancreas is normally protected from autodigestion by synthesis of pancreatic enzymes in the acinar cells in the proenzyme ​ form. 9 Precursor form of trypsin. (meaning preactivation of trypsin) ​ 5 Clinical Features: (Dr Al Humaidi said all of these are not important just focus on the first point). ​ ⭑ Abdominal pain10 is the cardinal manifestation of acute pancreatitis. Its severity varies from ​ mild to severe. - Characteristically, the pain is constant and intense and is often referred to the upper back. ​ ​ ​ ​ ​ • Leukocytosis, hemolysis. • Diffuse fat necrosis. • Full-blown acute pancreatitis is a medical emergency of the first magnitude. These patients usually ​ have the sudden onset of an "acute abdomen" that must be differentiated from diseases such as: ​ ​ ​ ​ - Ruptured acute appendicitis. - Perforated peptic ulcer. - Acute cholecystitis11 with rupture. - Occlusion of mesenteric vessels with infarction of the bowel. Laboratory findings: (very important) ​ marked elevation of serum amylase levels during the first 24 hours, followed within 72 to 96 hours by a ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ rising serum lipase level. Lipase is more specific, but needs more time to be elevated. ​ ​ ​ ​ ​ Management: • The key to the management is "resting the pancreas” by total restriction of food and fluids and by ​ ​ supportive therapy. • Most patients recover fully. About 5% die from shock during the first week of illness. ​ ​ ​ ​ Complications: (patient might be present by them directly as clinical manifestation). ​ ​ • Pancreatic pseudocyst. • Sterile Pancreatic abscess (neutrophil aggregation sterile not from infections). ​ ​ ​ • Shock: due to fluid sequestration12. • Peripheral vascular collapse. • Acute renal tubular necrosis. • Disseminated intravascular coagulation “DIS” (Fatal)13. ​ • Acute respiratory distress syndrome14 “ARDS” (Fatal). ​ 10 Radiates to the back. 11 inflammation of the gallbladder. ​ 12 ﺣﺒﺲ 13 Widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the ​ ​ ​ ​ ​ body. ​ 14 Because of the free destructive enzymes ​ 6 Chronic pancreatitis • Chronic pancreatitis is characterized by long standing inflammation of the pancreas with destruction of exocrine parenchyma, fibrosis, and, in the late stages the destruction of endocrine ​ parenchyma15. • The chief distinction between acute and chronic pancreatitis is the irreversible impairment in ​ ​ pancreatic function that is characteristic of chronic pancreatitis. Causes: • There is significant overlap in the causes of acute and chronic pancreatitis. Common causes Less common - Long term alcohol abuse. - Hypercalcemia, hyperlipidemia. - Long term biliary tract disease. - Long-standing obstruction of the pancreatic duct by pseudocysts, calculi, trauma, neoplasms, or ​ ​ These patients are usually middle-aged males. pancreas divisum16. ​ ​ - Tropical pancreatitis, which is a poorly ​ characterized disease seen in Africa and Asia. It has been attributed to malnutrition. - Hereditary pancreatitis (PRSS1 mutation ) ​ - Idiopathic chronic pancreatitis. - Recurrent bouts of acute pancreatitis may also be a cause. ​ 15 Will lead to diabetes mellitus. 16 Congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, ​ ​ ​ ​ ​ ​ 7 Morphology: Characterized by: • Parenchymal fibrosis. ​ • Reduced number and size of acini (acinar atrophy) with relative sparing of the islets of Langerhans. ​ ​ • Variable dilation of the pancreatic ducts. These changes are usually accompanied by a chronic inflammatory infiltrate around lobules and ducts. Grossly: gland is hard (because of extensive fibrosis), sometimes with extremely dilated ducts and visible ​ ​ ​ ​ calcification. Clinical Features: • Silent or recurrent attacks of abdominal pain, or persistent abdominal and back pain. ​ ​ • Attacks may be precipitated by alcohol abuse, overeating (which increases demand on the pancreas), or ​ ​ the use of opiates and other drugs. • During an attack of abdominal pain, there may be mild fever and mild-to-moderate elevations of serum ​ amylase. ​ • Calcifications can be seen within the pancreas by abdominal x ray. ​ ​ Complications: